食管癌個體化放射治療選擇性淋巴結(jié)區(qū)照射的價值

1、國內(nèi)食管癌照射范圍,? 局部照射野 傳統(tǒng)野 鋇片腫瘤部位、病變長度和食管軸向 常規(guī)野 鋇片所見加CT掃描 根據(jù)腫瘤實際范圍? 三維立體適形照射野(不規(guī)則野)? 精確放療調(diào)強照射野(多子野疊加，同期推量預(yù)防和治療)? 圖像引導(dǎo)生物信息調(diào)強(靶區(qū)內(nèi)劑量的不均勻化),照射野的具體范圍與勾畫,RTOG 85-01 (鱗癌占82%)放化組 鎖骨上區(qū)到食管胃結(jié)合部

2、 （下1/3段食管癌不照射鎖骨上區(qū)) 30Gy/15F后縮野到原腫瘤上下各 外放5cm再加20Gy/10F 總劑量50Gy單放組 原腫瘤上下各外放5cm 達50Gy/25F （胸上、中段食管癌照射鎖骨上區(qū)) 縮野至病變上下各外放5cm

3、再加14Gy /7F 總劑量64Gy,生存或 單放組 放化療結(jié)合組首次失敗 隨機62例 隨機61例（90年前) 非隨機69例(90后) 1年生存(%) 34% (21/62) 52%(32/61) 62%(4

4、3/69)3年生存(%) 0 30%(18/61) 18%(26/69)5年生存(%) 0 26%(14/61) 14%(10/69)中位生存 12

5、.2個月 14.1個月 16.7個月疾病未控率(%) 37%(23/62) 25%(15/61) 28%(19/69)局部區(qū)域失敗(%) 16%(10/62) 13%(8/61) 20%(14/69)

6、單純遠轉(zhuǎn)移(%) 15%( 6/62) 8%(5/61) 16%(11/69)局部+區(qū)域+遠轉(zhuǎn)(%) 15%(9/62) 8%(5/61) 10%(7/69),照射野的具體范圍與結(jié)果,RTOG 85-01長期結(jié)果,,,,,,低劑量組 腫瘤上下外放5cm、前后左右外放2cm照射

7、50.4 Gy （頸段癌包鎖骨上區(qū)，電子線補量 下段包腹腔干淋巴結(jié)區(qū)）高劑量組 前程同上達50.4Gy 后程縮野后為腫瘤上下各外放2cm 前后左右外放仍為2cm 總劑量64.8Gy,照射野的具體范圍與勾畫,RTOG 94-0

8、5 （二維放療）,照射野的具體范圍與結(jié)果,218例可供分析，高、低劑量組各109例，鱗癌占87%和84%中位隨訪16.4個月，生存者中位隨訪29.5個月治療相關(guān)死亡高劑量組和低組分別為10%(11 例) 和2%11例死亡者中，7例發(fā)生在≤50.4Gy過程中 3例在高劑量加量中 1例在結(jié)束64.8Gy后9個月瘺形成,RTO

9、G 94-05 長期結(jié)果,高劑量組109例 低劑量組109例中位生存期 13.0個月 18.1個月2年生存率 39% 40%局部區(qū)域失敗+未控 50% 55%遠轉(zhuǎn)移

10、 9% 16% 全部無差別,,,,,? 食管壁內(nèi)“多源性”病灶 Ｍiller 1/7的病例在主病灶2cm外可見繼發(fā)病灶 Pradoura 間隔≥5cm多源性癌達16% Reboud 多源性食管病變達35%? 淋巴結(jié)轉(zhuǎn)移 “跳躍式”轉(zhuǎn)移,關(guān)于食管癌多原發(fā)的研究,食管癌的生物學(xué)特

11、點： “跳躍性”,52例食管癌術(shù)后亞臨床病灶分布,亞臨床病灶 單純近端 單純遠端 上下兩端均有 總發(fā)生率(%)多中心起源 7例 3例 5例 15/52(28.9)重度不典型增生 11例 11例 6例 28/52(53.9)食管壁內(nèi)浸潤 12例

12、 10例 19例 41/52(78.9),,,,CTV縱向外放標(biāo)準(zhǔn)探討,史鴻云 祝淑釵 翟福山 《中華放射腫瘤學(xué)雜志》2006;15(4):280-284,多中心起源、壁內(nèi)浸潤和跳躍性轉(zhuǎn)移均可發(fā)生在距主瘤部位較遠的食管壁上,CTV縱向外放標(biāo)準(zhǔn)探討,這也是胸外科醫(yī)生要保證手術(shù)邊界的安全性 必須要切除較長的正常食管組織的主要原因,馬國偉，中華腫瘤雜志，2003，25(5): 472～474

13、史鴻云，中華放射腫瘤學(xué)雜志，2006，15(4)：280～284 Nishimaki T, World J Surg, 1996,20(1):32～37 Lam KY, Clinc Pathol,1996,49(2):124～129,食管癌生物學(xué)特點 淋巴結(jié)“跳躍式”轉(zhuǎn)移,,Details of recurrence sites after elective nodal irradiation (ENI) us

14、ing 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell carcinoma – A retrospective analysis Hideomi Yamashita, Kae Okuma, Reiko Wakui, Shino Kobayashi-Shibata,

15、 Kuni Ohtomo, Keiichi Nakagawa Department of Radiology, University of Tokyo Hospital, Hongo, Bunkyo-ku, Tokyo, JapanRadiotherapy and Oncology. 2011，98 ： 255–260,Details of rec

16、urrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell carcinoma – A retrospective analysis (Japan),,2000.6-2009.7

17、 126例鱗癌 中位年齡67歲 全部3DCRT 療前均PET 病變部位 胸上/胸中/胸下 29/53/44例 中位長度7.0cm 臨床分期 T1/T2/T3/T4 28/18/54/26例 N0/N1 50/76 M0/M1a/M1b 91/5/30 Ⅰ/Ⅱ/Ⅲ/Ⅳ 22/31/38/35

18、 (metastatic sites of M1b were lower cervical, supra-clavicular or celiac LNs) 化療方案 all patients received chemotherapy concurrently two cycles 5-flu

19、orouracil 800 mg/m2/day, days 1–4 & days 29–32 nedaplatin 80 mg/m2, day 1 & day 29 同期后再2 two cycles same dose chemotherapy,Radiotherapy and Onco

20、logy. 2011，98 ： 255–260,Definition regional LN by AJCC is mediastinal and perigastric LN excluding celiac LN. Definition of M1a region is cervical LNs in the upper thoracic, none in the middle thoracic, and celiac LNs

21、 in the lower thoracic esophagus,Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell carcinoma – A

22、retrospective analysis (Japan),GTV included primary tumor and LN 1 cm in short axis by CT or PET CTV was defined as the whole thoracic esophagus (from the supraclavicular fossae to the esophagogastric j

23、unction) including GTV plus 5 mm margin CTV comprised up to M1a LNs and regional LNs including positive LNs PTV adding margins 5–10 mm to the respective CTVs Mean lung D≤20 Gy V20

24、<20%. Spinal cord dose <45 Gy All patients ENI and were treated 50–50.4 Gy/1.8–2 Gy/5–5.6 W,結(jié)果 治療失敗 40例 單純局部復(fù)發(fā)20例 單純遠轉(zhuǎn)12例 局部+遠轉(zhuǎn)8例 選擇性淋巴引流

25、區(qū) 0例 局部失敗部位 上段失敗34%(10/29) 中段9% (5/53) 下段11% (5/44) P=0.0073(median period local recurrence 6.9 months)

26、 After CRT CR 69% (87/126) local residual tumor 31% (39/126) 失敗類型 16%(20/

27、126) local recurrence 47%(59/126) local recurrence and/or residual tumor 15%(19/126) distant failure

28、 38% (48/126) remained disease free,Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell

29、 carcinoma – A retrospective analysis (Japan),Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous

30、 cell carcinoma – A retrospective analysis (Japan),,結(jié)果 MTS 1年 2年 3年 總生存 28.5±6.9M 56% 43% 無病

31、生存 9.0±1.1M 46% 38% 33%,Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell

32、carcinoma – A retrospective analysis (Japan),,,,RTOG 85-0 ENI INT0123 no-ENI P valuelocal/regional failure and/or residual tumor 46% 55% 0.052-year survival

33、 36% 40% >0.05,Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for tho

34、racic esophageal squamous cell carcinoma – A retrospective analysis (Japan),large radiation fields used in this study was the fundamentaladherence to the first radiation field used in RTOG 85-01 and the results of mo

35、st surgical series in Japan have indicated a survival benefit of prophylactic 3-field LN dissection for SqCC in the thoracic esophagus,Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal

36、 radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell carcinoma – A retrospective analysis (Japan),ConclussionThis study suggest that ENI was effective for preventing regional nodal

37、 failure in CRT for esophageal SqCCmore local recurrences were detected in the upper thanin the middle and lower thoracic carcinomas,Retrospective Analysis of Outcome Differences in Preoperative Concurrent Chemoradiat

38、ion With or Without Elective Nodal Irradiation for Esophageal Squamous Cell Carcinoma Feng-Ming Hsu, M.D. Jang-Ming Lee, M.D., Ph.D , Pei-Ming Huang, M.D. Chia-Chi Lin, M.D., Ph.D. Chih-Hung Hsu, M.D., Ph.D. Yu-Chie

39、h Tsai, M.D. Yung-Chie Lee, M.D., Ph.D. Jason Chia-Hsien Cheng, M.D., Ph.DDepartment of Oncology, Department of Surgery ，National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei,

40、TaiwanInt.J. Radiat. Oncol.Biol.Physi. 2011, 81(4):593–599,Retrospective Analysis of Outcome Differences in Preoperative Concurrent Chemoradiation With or Without Elective Nodal Irradiation for Esophageal Squamous Ce

41、ll Carcinoma (Taiwan),回顧分析118例鱗癌 1997年AJCC分期Ⅱ和Ⅲ 術(shù)前同期放化療 放療劑量中位值36Gy 后行根治性切除 ENI 73例62%（鎖骨上預(yù)防 54例和腹腔引流區(qū)預(yù)防19例） IFI 45例38% 56例 57%接受同期化療（紫杉醇+順鉑，2周期） 隨訪遠處淋

42、巴結(jié)轉(zhuǎn)移包括(M1a 和M1b) 中位隨訪期38個月,材料,Retrospective Analysis of Outcome Differences in Preoperative Concurrent Chemoradiation With or Without Elective Nodal Irradiation for Esophageal Squamous Cell Carcinoma (Taiwan

43、),ENI組73例 IFI組45例 P值圍手術(shù)期死亡率 0.48≥3級心肺毒副反應(yīng) 0.44M1a 3年復(fù)發(fā)率

44、 3% 11% 0.05孤立遠LNM(M1a+M1b) 10% 14% 0.293年總生存率 45% 52% 0.313年無進展生存率

45、 45% 43% 0.89病理淋巴結(jié)轉(zhuǎn)移系總生存的獨立影響因素 HR=1.78 P=0.045,結(jié)果,結(jié)論 ENI 降低了M1a復(fù)發(fā)率但未改善生存，淋巴結(jié)轉(zhuǎn)移系影響因素,Radiotherapy and Oncology. 2009,92: 266–269,Elective nodal irradiation (ENI) in

46、definitive chemoradiotherapy(CRT) for squamous cell carcinoma of the thoracic esophagus,Masakatsu Onozawa a, Keiji Nihei a, Satoshi Ishikura c, Keiko Minashi b, Tomonori Yano b, Manabu Muto b, Atsushi Ohtsu b, Takashi O

47、gino a.,1999.2—2001.4 102例可分析的鱗癌 接受根治性放化同期 化療方案 DDP 40mg/m2 d1,d8 5-Fu 400mg/m2/d d1-5,d8-12 每5周重復(fù), 療中用2周期 療后劑量 DDP 80mg/m2 d1, 5-Fu 800mg/m2/d d1-5, 每4周重復(fù)放療

48、方案 CT診斷LNM為長徑≥1cm 范圍 胸上段包括鎖骨上, 胸下段包括腹腔在ENI野內(nèi) 前后兩野對穿 40Gy/20F/4W 休息2周后給予后程放療 斜野或多野 20Gy/10F/2W

49、 CTV包括原發(fā)瘤和轉(zhuǎn)移淋巴結(jié),上下外放3cm PTV包括原發(fā)瘤和轉(zhuǎn)移淋巴結(jié)和區(qū)域淋巴結(jié), 放1~1.5cm,所有病人中位隨訪17個月(3-62) 存活者 中位隨訪41個月(9-62)放化療后獲CR 62例占59% 其中40例生存 20例復(fù)發(fā)轉(zhuǎn)移3年總生存率43%,失敗模式 局部失敗即原發(fā)瘤復(fù)發(fā)累及淋巴結(jié)復(fù)發(fā)即原有

50、轉(zhuǎn)移的遠處失敗即除原發(fā)瘤和區(qū)域LNM外選擇淋巴結(jié)復(fù)發(fā)即在 ENI野內(nèi)的,Radiotherapy and Oncology. 2009,92: 266–269,Elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus,,Elective no

51、dal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus,In CRT for esophageal SCC ENI is effective for preventing regional nodal failureFurther evaluation of w

52、hether ENI leads to an improved overall survival is needed,結(jié) 論,Radiotherapy and Oncology. 2009,92: 266–269,Elective lymph node irradiation late course accelerated hyper-fractionated radiotherapy plus concurrent cispla

53、tin- based chemotherapy for esophageal squamous cell carcinoma: a phase II study Dongqing Wang, Jiali Yang, Jingyu Zhu, Baosheng Li, Limin Zhai， Mingping Sun, Heyi Gong, Tao Zhou, Yumei Wei, Wei Huang, Zhongtang

54、Wang, Hongsheng Li and Zicheng ZhangDepartment of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, China

55、 Radiation Oncology 2013, 8:108,Elective lymph node irradiation late course accelerated hyper-fractionated radiotherapy plus concurrent cisplatin based chemotherapy for esophageal squamous cell carcinoma: a phase I

56、I study,2004.1-2011.11 68例AJCC分期Ⅱ--Ⅳa 食管鱗癌 回顧性分析 中位年齡63歲(40-75) KPS≥80 頸段/胸上/胸中/胸下 8/24/27/9Ⅱ/Ⅲ/Ⅳa 分期為14/32/22 比例為 20.6% 、47.1% 、32.3% 2周期以DDP基礎(chǔ)同期化療 DDP+5-Fu

57、20例 占29.4% DDP+Capecitabine 12例 占17.5% DDP+ pemetrexed 32例 占47.1%,臨床材料,Elective lymph node irradiation late course

58、 accelerated hyper-fractionated radiotherapy plus concurrent cisplatin based chemotherapy for esophageal squamous cell carcinoma: a phase II study,放療方案,GTVp+GTVn GTVp 上下各外放5cm ,軸向外放1cm

59、 前程PTV1 GTVn 上下和軸向均外放0.8cm 高危淋巴引流區(qū)HRLNR 均勻外放0.8cm 處方劑量40Gy/20F/4W

60、 GTVp 上下各外放3cm ,軸向外放1cm 后程PTV2 GTVn 上下和軸向均外放0.8cm 不再照射高危淋巴引流區(qū)HRLNR

61、 19.6Gy/14F/1.4W 1.4Gy/F 2F/d 間隔>6h 前后兩程總劑量 59.6Gy/34F/5.4W,,,,,,,Elective lymph node irradiation late course accelerated hyper-fractionated radiotherapy plus concurrent cisplatin

62、 based chemotherapy for esophageal squamous cell carcinoma: a phase II study,Elective lymph node irradiation late course accelerated hyper-fractionated radiotherapy plus concurrent cisplatin based chemotherapy for eso

63、phageal squamous cell carcinoma: a phase II study,Elective lymph node irradiation late course accelerated hyper-fractionated radiotherapy plus concurrent cisplatin based chemotherapy for esophageal squamous cell carc

64、inoma: a phase II study,Elective lymph node irradiation late course accelerated hyper-fractionated radiotherapy plus concurrent cisplatin based chemotherapy for esophageal squamous cell carcinoma: a phase II study,Ele

65、ctive lymph node irradiation late course accelerated hyper-fractionated radiotherapy plus concurrent cisplatin based chemotherapy for esophageal squamous cell carcinoma: a phase II study,中位 隨訪18.5個月 中位生存34.4個月

66、 1年 3年 5年 P值總生存率 75.5% 46.5% 22.7%Ⅱ期和Ⅲ期總生存率 78.6% 49.4% 39.9% 0.671Ⅳa期總生存率 68.3% 41

67、.0% 15.4%,治療結(jié)果,首次失敗局部復(fù)發(fā) 20.6% 局部+區(qū)域失敗者29.4%(20/68) 區(qū)域失敗 17.6% 遠處轉(zhuǎn)移 19.1%≥3級急性食管炎和白細胞下降 26.4%(18/68)和32.4%(22/68)≥3級晚期損傷：食管狹窄1例，肺纖維化1例， 5例死于晚期并發(fā)癥(消化道出血3例，瘺2例),

68、,,,臨床資料1 2005.1---2010.12 食管癌患者219例接受放療 男144例,女75例,中位年齡67歲(40～89 歲)2 根據(jù)是否采用淋巴引流區(qū)放療分為 預(yù)防野組114例，累及野組105例 3 臨床分期采用 2009 年中國非手術(shù)治療食管 專家小組提出的 《非手術(shù)治療食管癌臨床分期標(biāo)準(zhǔn)》,入組條件1 病理或細胞學(xué)證實的食管癌患者 2 進流食或半流食,卡氏評分≥70分